The proposed research is designed to provide a basic understanding of the role of persisting antigen in the regulation and maintenance of the immune response. Polymerized human serum albumin, the antigen used in this system, is capable of persisting in rabbits for at least a year, and it is capable of spontaneously stimulating a secondary response in cell cultures prepared from the lymph nodes of immunized rabbits. Induction of this response is subject to an antibody feedback mechanism. In an effort to determine the mechanism of antibody feedback, experiments are planned using different classes and fragments of antibodies as well as fractionated lymphoid cells and complement. The mechanism may be as simple as antibody masking persisting antigen or it may be much more complex. Persisting antigen appears to be associated with macrophages and the proposed research is designed to determine the nature of this association. Experiments will be undertaken to determine if macrophages serve simply as an antigen depot or if they must process and present antigen in some special way. Localization of polymerized HSA in draining lymph nodes is striking even though memory cells are present in non-draining lymph nodes. Various forms of HSA will be compared to determine how modification of the HSA molecule affects antigen localization and persistence as well as induction and maintenance of the immune response.